PMID- 22219324 OWN - NLM STAT- MEDLINE DCOM- 20120611 LR - 20120120 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 188 IP - 3 DP - 2012 Feb 1 TI - Vitamin D receptor gene polymorphisms and HLA DRB1*04 cosegregation in Saudi type 2 diabetes patients. PG - 1325-32 LID - 10.4049/jimmunol.1101954 [doi] AB - The vitamin D receptor (VDR) gene has been involved in the modulation of susceptibility to inflammatory and autoimmune conditions, and could play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). Susceptibility to T2DM was recently also suggested to associate with HLA alleles. We evaluated possible correlations between VDR polymorphisms, HLA alleles, and risk for development of T2DM by analyzing 627 individuals (368 T2DM patients and 259 healthy control subjects) part of a well-characterized cohort followed in Riyadh, Kingdom of Saudi Arabia. Genomic DNA was genotyped for the VDR gene single nucleotide polymorphisms of Fok-1, Taq-1, ApaI, and Bsm-I. Analyses were run by allelic discrimination real-time PCR. HLA genotyping was performed as well by PCR using sequence-specific primers, whereas cytokine production was evaluated by FACS. Results showed T2DM to be significantly associated with the VDR Taq1 (rs731236-AG) and Bsm-I (rs1544410-CT) genotypes, and the VDR rs1544410-T allele. Cosegregations resulting in significant increases of T2DM odds ratio were detected between Taq1 and Bsm-I VDR polymorphisms and HLA DRB1*04. Notably, the VDR polymorphisms observed to be more frequent in T2DM patients correlated with increased VDR expression and IL-12 production, as well as with metabolic parameters of susceptibility to T2DM, including serum cholesterol and high-density lipoprotein levels. VDR polymorphisms are present in T2DM, and correlate with HLA DRB1*04 and with immunologic and metabolic parameters; results from this study add T2DM to the list of diseases that are likely modulated by an HLA/VDR interaction. FAU - Al-Daghri, Nasser M AU - Al-Daghri NM AD - Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia. aldaghri2011@gmail.com FAU - Al-Attas, Omar AU - Al-Attas O FAU - Alokail, Majed S AU - Alokail MS FAU - Alkharfy, Khalid M AU - Alkharfy KM FAU - Draz, Hossam M AU - Draz HM FAU - Agliardi, Cristina AU - Agliardi C FAU - Mohammed, Abdul Khader AU - Mohammed AK FAU - Guerini, Franca R AU - Guerini FR FAU - Clerici, Mario AU - Clerici M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120104 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (HLA-DRB1 Chains) RN - 0 (Receptors, Calcitriol) SB - IM MH - Case-Control Studies MH - Chromosome Segregation MH - Diabetes Mellitus, Type 2/epidemiology/*genetics MH - Disease Susceptibility MH - Genetics, Population MH - HLA-DRB1 Chains/*genetics MH - Humans MH - *Polymorphism, Genetic MH - Receptors, Calcitriol/*genetics MH - Saudi Arabia/epidemiology EDAT- 2012/01/06 06:00 MHDA- 2012/06/12 06:00 CRDT- 2012/01/06 06:00 PHST- 2012/01/06 06:00 [entrez] PHST- 2012/01/06 06:00 [pubmed] PHST- 2012/06/12 06:00 [medline] AID - jimmunol.1101954 [pii] AID - 10.4049/jimmunol.1101954 [doi] PST - ppublish SO - J Immunol. 2012 Feb 1;188(3):1325-32. doi: 10.4049/jimmunol.1101954. Epub 2012 Jan 4.